Eucalyptol suppresses matrix metalloproteinase-9 expression through an extracellular signal-regulated kinase-dependent nuclear factor-kappa B pathway to exert anti-inflammatory effects in an acute lung inflammation model

J Pharm Pharmacol. 2015 Aug;67(8):1066-74. doi: 10.1111/jphp.12407. Epub 2015 Mar 13.

Abstract

Objectives: The acute lung injury (ALI) model is characterised by a severe acute inflammatory response in the lungs that represents the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we sought to elucidate the anti-inflammatory mechanism of eucalyptol in relation to tissue remodelling in acute lung inflammation.

Methods: BALB/C mice were intraperitoneally injected with eucalyptol (100, 200 or 400 mg/kg) or dexamethasone (1 mg/kg) 1 h before intratracheal challenge with lipopolysaccharide (LPS; 1.5 mg/kg) and sacrificed after 4 h. The anti-inflammatory effects of eucalyptol were assessed by determining cell counts, measuring cytokine and nitric oxide production and performing Western blotting and histological analyses.

Key findings: Eucalyptol attenuated inflammation-associated increases in cell numbers, matrix metalloproteinase-9 (MMP-9) expression, production of cytokines (tumour necrosis factor-α and interleukin-6) and nitric oxide, and nuclear factor-kappa B (NF-κB) and phosphorylated extracellular signal-regulated kinase protein levels induced by LPS in bronchoalveolar lavage fluid from ALI mice. Furthermore, pretreatment with 400 mg/kg eucalyptol prevented LPS-induced histopathological changes. Collectively, these results indicate that eucalyptol acts through a mechanism involving decreased MMP-9 expression and an extracellular signal-regulated kinase-dependent NF-κB pathway to exert anti-inflammatory actions in acute lung inflammation.

Conclusions: Thus, eucalyptol may be a potentially important agent in the treatment of pulmonary inflammation.

Keywords: LPS; MMP-9; NF-κB; acute lung injury; eucalyptol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / physiopathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cyclohexanols / pharmacology*
  • Cytokines / biosynthesis
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Drug Dosage Calculations
  • Eucalyptol
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis*
  • Lipopolysaccharides / pharmacology
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Monoterpenes / pharmacology*
  • NF-kappa B / biosynthesis*
  • Nitric Oxide / biosynthesis
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Cyclohexanols
  • Cytokines
  • Lipopolysaccharides
  • Monoterpenes
  • NF-kappa B
  • Nitric Oxide
  • Dexamethasone
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 9
  • Eucalyptol